MONOCLONAL ANTIBODIES

5 Jun

Monoclonal antibodies are  a more recent approach to antiviral immunotherapy. These antibodies have been  developed for viruses such  as HIV, although extensive evaluation has  yet to be undertaken. A specific  monoclonal antibody against cellu- lar  IL-2 receptors (daclizumab) has  been  developed and  eval- uated for the  prevention of graft rejection in renal transplant recipients (356). In these graft recipients, daclizumab led to a decreased incidence of CMV infection when added to conven- tional dual immunosuppressive therapy, but  had  no  effect when added to  triple therapy. Additional development and studies will be needed.

The  only  licensed form  of monoclonal antibodies avail- able  is  palivizumab  (Synagis) for  RSV  infection. This  is  a humanized preparation of monoclonal antibodies directed at the  F  glycoprotein, a  specific  surface protein of RSV  (357). Because palivizumab is not produced from human blood prod- ucts, it carries no risk of infectious contamination. Adminis- tration of the  preparation is  more  convenient than RSV-IG, requiring 1  intramuscular injection rather than a  4-hour intravenous infusion of the  hyperimmune globulin. In  addi- tion, product shortages are  not expected since  the  preparation can easily be produced in large batches.

In  a large, placebo-controlled clinical trial of high-risk infants, palivizumab led  to a 55% reduction in  RSV hospi- talization, a 42% reduction in the  number of hospitalization days, and  a 57% reduction in  intensive-care unit days  due to  RSV  infection (358).  Adverse effects  are  rare and  mini- mal.  When comparing palivizumab and  placebo, there were no significant differences in  the  rates of side  effects  or the development of antibodies to  monoclonal antibody  (359), but  an increase in aminotransferase levels  was  noted in the palivizumab  group compared with  placebo (290).  Viral resistance has  not  yet  been  detected with the  use  of palivi- zumab (360).

CONCLUSION

The implementation of routine immunizations not only has  a significant impact on  the  overall incidence of disease, but also  markedly decreases the  direct and  indirect costs  associ- ated with health care.  For  instance, a 1994  study on the  cost- effectiveness of a varicella vaccination program in the  United States estimated a savings of $384 million per year (361). The cost  savings with varicella are  mostly due  to  a  decrease in time lost from work by caregivers, although this is significant. Vaccines for more  serious diseases that often  require hospital- ization, such  as RSV in infants, will likely  result in a more  ben- eficial  cost-effective profile. The cost savings of the  eradication of  smallpox, a  disease  which killed millions of  people, approaches the  level of infinity when considering the  millions more  that would  have been  affected. A similar situation exists for poliomyelitis, which is expected to be eradicated worldwide in the  near future. The cost savings for an HIV vaccine would also  be  phenomenal, when considering the  long-term treat- ment and  numerous complications that are  involved with this chronic infection.

Immunization has  successfully led  to  the  reduction in incidence of numerous diseases. Careful development and clinical evaluation have provided safe  and  effective vaccines with few adverse effects. Many reported adverse reactions fol- lowing  vaccination may  be  coincidental and  have no  proven direct relationship with the  vaccine in  question. Although serious side  effects  may  rarely occur  from  vaccines, a  much greater risk for morbidity and  mortality results from  the  fail- ure to become  immunized. One vaccine, however, was recently removed from  the  market due  to  safety issues. Rotashieldâ was  a live, oral  tetravalent, rotavirus vaccine that was  associ- ated with several cases of intussusception and  is considered to be causal (362).

Most  associations between vaccines and  adverse events are  not, however, demonstrated to be causal. For example, the measles mumps rubella (MMR) vaccine was reported recently not  to  have a  causal relationship to  autism  (363,364). Like- wise,  a  causal relationship between the  hepatitis B vaccine and  a  variety of autoimmune diseases has  been  disproven. This  vaccine does  not  increase the  risk of multiple sclerosis (365) nor  does  it cause a relapse of preexisting multiple scle- rosis  (366).  Nevertheless, suspected relationships between vaccines and  adverse events need  to be reported to the  “Vac- cine  Adverse Event  Reporting System” (1-800-822-7967) so that the excellent safety record of vaccines can be maintained.

The  technology of vaccine development  has  progressed dramatically in  the  last decade. While  more  conventional methods have consisted of whole-killed or  live-attenuated viruses, more  recent advancements include genetically engi- neered vectors and  virus-like particles, among many others. Anticipated vaccine developments in the  future show  exciting promise in several areas, such  as  immunization with plants.

Potatoes, tomatoes, and  bananas are  currently undergoing genetic engineering to express immunizing antigens against infections such  as  hepatitis B virus and  Norwalk virus (367,

368). This  form  of vaccination would  offer a convenient, pain- less,  and  inexpensive approach to widespread control of dis- ease  and  would  thus be accessible to developing countries.

It is anticipated that the  future will bring safe  and  effec- tive vaccines for a variety of viral diseases, e.g., HIV, hepatitis C, HSV,  and  HPV.  Although no  vaccine is  available for  the therapy of a viral disease, the  concept of vaccines is now being expanded by  ongoing clinical trials  of therapeutic vaccines, e.g., for HIV, HSV, and  HPV.

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